Recently, people have increasingly tendered to over-ingest cholesterol. As a result, diseases associated with cholesterol are increasingly becoming a big social problem. In particular, Eastern people, who have experienced westernization of their lifestyles, including their diet, have far more opportunities to consume high cholesterol foods than before on account of the deluge of instant or fast foods. When being ingested, the cholesterol of such foods increases the cholesterol level in blood and may act as a main cause of cardiovascular diseases, including hyperlipidemia, arteriosclerosis, arrhythmia, cardiac infarction, and so on.
Through studies of the metabolism of cholesterol, it has been shown that both endogenic and dietary cholesterol move into the small intestine and about 50% thereof is absorbed from the intestines (Bosner, M. S., Ostlund, R. E., Jr., Osofisan, O., Grosklos, J., Fritschle, C., Lange, L. G. 1993). Based on this fact, a mechanism for preventing cholesterol from being absorbed from intestines is of special interest to those who have made efforts to discover clues for the prophylaxis and treatment of cholesterol-associated diseases.
Plant sterol or phytosterol can be broken down into sitosterol, campesterol, and stigmasterol, while plant stanol or phytostanol comprises sitostanol and campestanol. For purposes of convenience, they are all called plant sterol herein.
With structures very similar to that of cholesterol, plant sterol is known to inhibit intestinal cholesterol absorption, thereby reducing the serum cholesterol level, as disclosed in U.S. Pat. No. 5,578,334. Being a naturally occurring material, plant sterol is non-toxic and can be found in a broad spectrum of plants such as bean, corn, wood, tall oil, etc. By taking advantage of the inhibitory function of plant sterol against intestinal cholesterol absorption, clinical trials have been conducted of plant sterol as a therapeutic agent for treatment of cardiovascular diseases, coronary artery diseases and hyperlipidemia (Atherosclerosis 28:325-338).
Despite this useful function, plant sterol is difficult to apply to foods on account of its physical properties, that is, very poor solubility in both water and oil. Accordingly, the general public can only limitedly ingest plant sterol.
With the aim of increasing the solubility of plant sterol, some researchers have synthesized various derivatives of plant sterol. For example, ester forms of plant sterol were developed, which have excellent solubility in oil phases (Mattson F. H., R. A. Volpenhein, and B. A. Erickson, 1997). In U.S. Pat. No. 5,502,045, sitostanol fatty acid ester is disclosed which is prepared by the interesterification of sitostanol with a fatty acid. According to this patent, the sitostanol fatty acid ester is reported to reduce the LDL-C level by as much is 16% when being used in an applied form in an oil phase (margarine).
WO 99/15546 and WO 99/15547 describe water- and oil-soluble plant sterol derivatives which are synthesized by linking a water- or oil-soluble molecule to plant sterol or plant stanol via an ester linkage.
However, a research result reveals that synthetic plant sterol derivatives with improved solubility have lower inhibitory effect on intestinal cholesterol absorption than does natural plant sterol (Mattson et al., The American Journal of Clinical Nutrition 35: April 1982 pp 697-700). Particularly, such oil-soluble derivatives are disadvantageous in that a lot of edible oil must also be ingested at the same time.
In addition to the effort to increase the solubility of plant sterol through the synthesis of derivatives, intensive research has been and continues to be directed to improving the bioavailability of plant sterol.
Much has been done with regard to this research. For instance, a pharmaceutical dispersible powder of sitosterols for oral administration was developed which can be prepared from a mixture of sitosterol, starch hydrolysate, silicon dioxide, and polyoxylene sorbitan monostearate in a certain proportion by homogenization, deaeration, pasteurization, and evaporation, as disclosed in U.S. Pat. No. 3,881,005.
Disclosed in U.S. Pat. No. 5,932,562 is an aqueous homogeneous micellar mix of a plant sterol, lecithin and lysolecithin which has been dried to a finely divided water soluble powder. This was obtained by mixing plant sterol lecithin and lysolecithin together in chloroform at a fixed molar ratio and removing the chloroform therefrom. In this patent however, some problems are inherent. The total amount of the emulsifiers used in the patent is greater than that of the plant sterol. The emulsifier lysolecithin is very expensive. What is worse, the organic solvent used to form the micelles makes the water-soluble powder unsuitable for ingestion.
Other water-soluble plant sterols can be found in U.S. Pat. Nos. 6,054,144 and 6,110,502. According to these patents, aqueous-dispersible plant sterol is produced by admixing oryzanol or plant sterol, a monofunctional surfactant and polyfunctional surfactant in water at fixed ratios, and drying the admixture. This production method is characterized by being free from homogenization and deaeration steps with adoption of polyoxylene sorbitan monopalmitate and sorbitan monopalmitate as a monofunctional surfactant and a polyfunctional surfactant, respectively.
In European Pat Publication No. 289,636 is described a method of producing emulsified or solubilized sterol in a stable form by admixing plant sterol at a fixed ratio with a liquid polyhydroxy compound containing sucrose fatty acid ester and/or polyglycerol fatty acid ester and diluting the admixture with water. When being applied to drinks, micelle particles of the plant sterol produced amount, in size, to as large as tens of micrometers, being bristly to the feel of the mouth. Furthermore, the micelle particles have the disadvantage of making the drinks opaque.
A food ingredient that can be used as a cholesterol-lowering agent is disclosed in U.S. Pat. No. 6,190,720. This patent also introduced the preparation of the food ingredient by combining one or more molten plant sterols with one or more fats and one or more emulsifiers to homogeneity and cooling the homogeneous mixture to about 60° C. under agitation to give a paste. This food ingredient can be applied to oil-based foods such as salad dressings, margarine, etc. As expected, the applicability of the food ingredient to aqueous beverages is virtually impossible because its dispersion stability is obtained only in fats.
EP 0 897 671 A1 is directed to aqueous dispersions of plant sterols useful in spreads, dressings, milk, cheese, etc, and to a preparation method comprising mixing together a molten high melting lipid, a non-sterol emulsifier and water under shear with a feature residing in that the high melting lipid has a mean size of 15 microns or less. The aqueous dispersions enjoy the advantage of permitting minimization or elimination of saturated fats and trans fatty acids. However, micronization of high melting lipids such as plant sterol must be conducted. In addition, the dispersion is not applied to aqueous beverages because of its low dispersion stability.
Cholesterol reducing, edible products can be found in WO 00/33669. According to the method of this patent, plant sterols are dissolved or mixed in a melt of a food emulsifier, admixed with proteineous foods such as milk or yogurt, homogenized, and added to food products. The dispersion stability of the cholesterol reducing, edible products is maintained only in the presence of a proteineous material, but not maintained in the absence of a proteineous material. Therefore, it is very difficult to apply the cholesterol reducing, edible products to beverages free of proteineous materials.
U.S. Pat. No. 6,267,963 is concerned with a plant sterol-emulsifier complex which has a melting temperature at least 30° C. below that of the plant sterol, characterized in that, due to its reduced melting temperature, the plant sterol-emulsifier is less likely to crystallize during or after the manufacture of food products and can be incorporated into food products in an amount effective to reduce serum cholesterol levels in a human consuming the food products without adversely modifying the texture of the food products. Prepared from plant sterols, emulsifiers, and neutral lipids such as triglycerides, the complex can be applied to oil-based food products. In the absence of neutral lipids, sodium stearoyl lactylate is employed as an emulsifier. However, the use of sodium stearoyl lactylate is limited by law. Additionally, its characteristic offensive odor requires a masking process when the complex is applied to beverages.